Calcium(II)-Catalyzed off-/on-DNA Reductive Deuteration Amination in HFIP: Modular Access to N-α-Deuterated Amino Acids

Calcium(II)-Catalyzed off-/on-DNA Reductive Deuteration Amination in HFIP: Modular Access to N-α-Deuterated Amino Acids | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Calcium(II)-Catalyzed off-/on-DNA Reductive Deuteration Amination in HFIP: Modular Access to N-α-Deuterated Amino Acids Shengdong Wang, Haoran Li, Yuwei Liu, Silin Zhang, Lei Ma, Zhongyi Zeng, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4944895/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Feb, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract The development of practical and selective deuterium incorporation strategies for building deuterated molecules, especially deuterium-labeled amino acids, has become an increasing focus in basic research, but still remains challenging. We herein report a bioinspired calcium(II)/HFIP-catalyzed site-selective modular reductive deuteration amination of simple keto acids/esters with amines by using d2-Hantzsch ester as the deuterium source, delivering N-α-deuterated amino acid motifs in a remarkable deuteration efficiency (>99 deuterated ratio) and with diverse functionality (>130 examples), for which various substrates, especially including amino acids, peptides, drug molecules and natural products bearing different substituted forms, was found to be well compatible. Besides, the application of this strategy in the on-DNA synthesis of DNA-tagged N-α-deuterated amino acids/peptides has been exemplified. The work provides an efficient and innovative solution for deuterated amino acid chemistry and should have a robust application potential in organic synthesis, medicinal chemistry and chemical biology. Physical sciences/Chemistry/Catalysis/Homogeneous catalysis Physical sciences/Chemistry/Chemical biology/DNA Full Text Additional Declarations There is NO Competing Interest. Supplementary Files CCDC2349502.cif CCDC 2349502 SupplementaryInformation.pdf CCDC2288911.cif CCDC 2288911 Cite Share Download PDF Status: Published Journal Publication published 20 Feb, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4944895","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":345119193,"identity":"22b5de0c-534d-47ab-b213-d683289270dd","order_by":0,"name":"Shengdong 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